Heat and moisture exchangers versus heated humidifiers for mechanically ventilated adults and children

Donna Gillies; David A Todd; Jann P Foster; Bisanth T Batuwitage

doi:10.1002/14651858.CD004711.pub3

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Figure 1

Study flow diagram.

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Figure 2

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Figure 3

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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Figure 4

Funnel plot of comparison: 1 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ parallel studies, outcome: 1.1 Artificial airway occlusion.

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Figure 5

Funnel plot of comparison: 1 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ parallel studies, outcome: 1.2 Mortality.

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Figure 6

Funnel plot of comparison: 1 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ parallel studies, outcome: 1.3 Pneumonia.

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Analysis 1.1

Comparison 1 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ parallel studies, Outcome 1 Artificial airway occlusion.

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Analysis 1.2

Comparison 1 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ parallel studies, Outcome 2 Mortality.

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Analysis 1.3

Comparison 1 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ parallel studies, Outcome 3 Pneumonia.

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Analysis 1.4

Comparison 1 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ parallel studies, Outcome 4 Atelectasis.

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Analysis 1.5

Comparison 1 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ parallel studies, Outcome 5 Tracheal aspirations (per day).

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Analysis 1.6

Comparison 1 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ parallel studies, Outcome 6 Saline instillations (number per day).

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Analysis 1.7

Comparison 1 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ parallel studies, Outcome 7 Change in body temperature (absolute data) (ºC).

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Analysis 1.8

Comparison 1 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ parallel studies, Outcome 8 Change in body temperature mean data) (ºC).

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Comparison 2 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ cross‐over studies, Outcome 1 PaO2 (mmHg).

Analysis 2.1

Comparison 2 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ cross‐over studies, Outcome 1 PaO₂ (mmHg).

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Comparison 2 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ cross‐over studies, Outcome 2 PaCO2 (mmHg).

Analysis 2.2

Comparison 2 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ cross‐over studies, Outcome 2 PaCO₂ (mmHg).

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Analysis 2.3

Comparison 2 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ cross‐over studies, Outcome 3 Breathing rate (breaths/minute).

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Analysis 2.4

Comparison 2 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ cross‐over studies, Outcome 4 Tidal volume (L).

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Analysis 2.5

Comparison 2 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ cross‐over studies, Outcome 5 Minute ventilation (L/minute).

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Analysis 2.6

Comparison 2 Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ cross‐over studies, Outcome 6 Body temperature (ºC).

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Analysis 3.1

Comparison 3 Subgroup analysis ‐ children versus adults, Outcome 1 Artificial airway occlusion.

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Analysis 3.2

Comparison 3 Subgroup analysis ‐ children versus adults, Outcome 2 All‐cause mortality.

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Analysis 4.1

Comparison 4 Subgroup analysis ‐ length of ventilation, Outcome 1 Artificial airway occlusion.

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Analysis 4.2

Comparison 4 Subgroup analysis ‐ length of ventilation, Outcome 2 All‐cause mortality.

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Analysis 4.3

Comparison 4 Subgroup analysis ‐ length of ventilation, Outcome 3 Pneumonia.

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Analysis 5.1

Comparison 5 Subgroup analysis ‐ hygroscopic versus hydrophobic heat and moisture exchanger (HME), Outcome 1 Artificial airway occlusion.

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Analysis 5.2

Comparison 5 Subgroup analysis ‐ hygroscopic versus hydrophobic heat and moisture exchanger (HME), Outcome 2 All‐cause mortality.

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Analysis 5.3

Comparison 5 Subgroup analysis ‐ hygroscopic versus hydrophobic heat and moisture exchanger (HME), Outcome 3 Pneumonia.

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Analysis 6.1

Comparison 6 Heat and moisture exchanger (HME) with and without filters, Outcome 1 Artificial airway occlusion.

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Analysis 6.2

Comparison 6 Heat and moisture exchanger (HME) with and without filters, Outcome 2 All‐cause mortality.

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Analysis 6.3

Comparison 6 Heat and moisture exchanger (HME) with and without filters, Outcome 3 Pneumonia.

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Analysis 7.1

Comparison 7 Sensitivity analyses ‐ selection bias, Outcome 1 Mortality.

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Analysis 7.2

Comparison 7 Sensitivity analyses ‐ selection bias, Outcome 2 Pneumonia.

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Analysis 8.1

Comparison 8 Sensitivity analyses ‐ detection bias, Outcome 1 Artificial airway occlusion.

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Analysis 8.2

Comparison 8 Sensitivity analyses ‐ detection bias, Outcome 2 Pneumonia.

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Summary of findings for the main comparison. Heat and moisture exchangers (HME) compared to heated humidifiers (HH) for ventilated adults and children

Heat and moisture exchangers (HME) compared to heated humidifiers (HH) for ventilated adults and children
Patient or population: ventilated adults (18 trials) and children (1 trial) Settings: ICUs (17), NICU (1), and hospitals (1) in France (7), USA (3), Australia (2), Brazil (2), Denmark (1), Italy (1), Saudi Arabia (1), Spain (1), Switzerland (1) Intervention: HME Comparison: HH
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	HH	HME
Artificial airway occlusion (measured over 3‐15 days (median 4 days))	23 per 1000	37 per 1000	RR 1.59 (0.6 to 4.19)	2171 (15 studies)	⊕⊕⊝⊝ ¹ L ow	Allocation and blinding unclear in 13 studies; moderate heterogeneity.
Mortality ‐ all cause (Measured over 3‐15 days (median 8 days))	247 per 1000	257 per 1000	RR 1.03 (0.89 to 1.20)	1951 (12 studies)	⊕⊕⊝⊝ ² L ow	Allocation and blinding unclear in 9 and 11 studies; low heterogeneity.
Pneumonia (Measured over 4‐21 days (median 4 days))	32 per 1000	30 per 1000	RR 0.93 (0.73 to 1.19)	2251 (13 studies)	⊕⊕⊝⊝ ³ L ow	Allocation and blinding unclear in more than half of studies; moderate heterogeneity though this was due to only 1 study.
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: 95% confidence interval; HH: heated humidification; HME: heat and moisture exchanger; ICU: intensive care unit; NICU: neonatal intensive care unit; RR: risk ratio.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
The assumed and corresponding risks were calculated from data in included trials. ¹ Quality downgraded two levels for serious indirectness because participants may not have been considered suitable for HME in three studies and could be taken out of the HME group in three studies. ² Quality downgraded two levels for serious indirectness because participants may not have been considered suitable for HME in two studies and could be taken out of the HME group in three studies. ³ Quality downgraded two levels for serious indirectness because participants may not have been considered suitable for HME in two studies and could be taken out of the HME group in three studies.

Summary of findings for the main comparison. Heat and moisture exchangers (HME) compared to heated humidifiers (HH) for ventilated adults and children

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Table 1. Length of stay ‐ intensive care unit (mean days)

Study	HH	HME	No of participants
Boots 2006	9	7	381
Diaz 2002	4	4	43
Hurni 1997	13.80	11.10	104
Kollef 1998	5.30	5.70	310
Lacherade 2005	25.3	21.4	369
Roustan 1992	9.30	13.90	116
HH: heated humidification; HME: heat and moisture exchangers.

Table 1. Length of stay ‐ intensive care unit (mean days)

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Table 2. Length of stay ‐ hospital (mean days)

Study	HH	HME	No of participants
Diaz 2002	11	10	43
Kollef 1998	16.50	16.50	310
HH: heated humidification; HME: heat and moisture exchangers.

Table 2. Length of stay ‐ hospital (mean days)

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Table 3. Cost

Study	HME	HH	Units	Participants
Boots 1997	6.72	8.20	AUD/day	83
Boots 2006	8.62	9.27	AUD/day	381
Branson 1996	4.70	8.97	USD/day	99
Dreyfuss 1995	5.00	11.00	USD/day (France)	131
Kirton 1997	17.46	27.80	USD/participant	280
Kollef 1998	15.98	38.26	USD/participant	310
HH: heated humidification; HME: heat and moisture exchangers.

Table 3. Cost

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Table 4. Work of breathing (joules/minute ‐ mean)

Study	HH	HME	Participants
Girault 2003	9.86	16.50	11
Iotti 1997	13.6	20.8	10
HH: heated humidification; HME: heat and moisture exchangers.

Table 4. Work of breathing (joules/minute ‐ mean)

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Comparison 1. Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ parallel studies

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Artificial airway occlusion Show forest plot	15	2171	Risk Ratio (M‐H, Random, 95% CI)	1.59 [0.60, 4.19]

2 Mortality Show forest plot	12		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 All cause	12	1951	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.89, 1.20]
2.2 Pneumonia‐related	3	484	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.39, 3.01]
3 Pneumonia Show forest plot	13	2251	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.73, 1.19]

3.1 Throughout ventilation	7	1090	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.69, 1.27]
3.2 ≥ 48 hours after ventilation	6	1161	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.64, 1.46]
4 Atelectasis Show forest plot	3	303	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.52, 1.40]

5 Tracheal aspirations (per day) Show forest plot	3	290	Mean Difference (IV, Random, 95% CI)	‐0.47 [‐1.41, 0.47]

6 Saline instillations (number per day) Show forest plot	3	276	Std. Mean Difference (IV, Random, 95% CI)	‐0.40 [‐0.64, ‐0.17]

7 Change in body temperature (absolute data) (ºC) Show forest plot	6	321	Mean Difference (IV, Random, 95% CI)	‐0.49 [‐0.96, ‐0.02]

8 Change in body temperature mean data) (ºC) Show forest plot	3	78	Mean Difference (IV, Random, 95% CI)	‐0.59 [‐0.82, ‐0.36]

Comparison 1. Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ parallel studies

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Comparison 2. Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ cross‐over studies

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 PaO₂ (mmHg) Show forest plot	4		Mean Difference (Random, 95% CI)	Subtotals only

1.1 r = 0.3	4		Mean Difference (Random, 95% CI)	‐3.24 [‐16.08, 9.60]
1.2 r = 0.5	4		Mean Difference (Random, 95% CI)	‐3.87 [‐16.73, 9.00]
1.3 r = 0.7	4		Mean Difference (Random, 95% CI)	‐4.41 [‐17.09, 8.27]
2 PaCO₂ (mmHg) Show forest plot	5		Mean Difference (Random, 95% CI)	Subtotals only

2.1 r = 0.3	5		Mean Difference (Random, 95% CI)	1.93 [0.27, 3.59]
2.2 r = 0.5	5		Mean Difference (Random, 95% CI)	2.02 [0.19, 3.85]
2.3 r = 0.7	5		Mean Difference (Random, 95% CI)	2.21 [0.33, 4.09]
3 Breathing rate (breaths/minute) Show forest plot	4		Mean Difference (Random, 95% CI)	Subtotals only

3.1 r = 0.3	4		Mean Difference (Random, 95% CI)	1.40 [0.33, 2.46]
3.2 r = 0.5	4		Mean Difference (Random, 95% CI)	1.15 [‐0.13, 2.44]
3.3 r = 0.7	4		Mean Difference (Random, 95% CI)	1.02 [‐0.38, 2.41]
4 Tidal volume (L) Show forest plot	5		Mean difference (Random, 95% CI)	Subtotals only

4.1 r = 0.3	5		Mean difference (Random, 95% CI)	0.02 [‐0.00, 0.03]
4.2 r = 0.5	5		Mean difference (Random, 95% CI)	0.02 [0.00, 0.04]
4.3 r = 0.7	5		Mean difference (Random, 95% CI)	0.03 [0.01, 0.06]
5 Minute ventilation (L/minute) Show forest plot	5		Mean difference (Random, 95% CI)	Subtotals only

5.1 r = 0.3	5		Mean difference (Random, 95% CI)	1.20 [0.78, 1.61]
5.2 r = 0.5	5		Mean difference (Random, 95% CI)	1.19 [0.63, 1.75]
5.3 r = 0.7	5		Mean difference (Random, 95% CI)	1.18 [0.55, 1.80]
6 Body temperature (ºC) Show forest plot	2		Mean Difference (Random, 95% CI)	Subtotals only

6.1 r = 0.3	2		Mean Difference (Random, 95% CI)	‐1.12 [‐3.77, 1.52]
6.2 r = 0.5	2		Mean Difference (Random, 95% CI)	‐1.13 [‐3.77, 1.52]
6.3 r = 0.7	2		Mean Difference (Random, 95% CI)	‐1.13 [‐3.78, 1.51]

Comparison 2. Heat and moisture exchanger (HME) versus heat humidifier (HH) ‐ cross‐over studies

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Comparison 3. Subgroup analysis ‐ children versus adults

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Artificial airway occlusion Show forest plot	15		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Children	1	56	Risk Ratio (M‐H, Random, 95% CI)	0.64 [0.33, 1.26]
1.2 Adults	14	2115	Risk Ratio (M‐H, Random, 95% CI)	1.94 [0.65, 5.76]
2 All‐cause mortality Show forest plot	12		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Children	1	56	Risk Ratio (M‐H, Random, 95% CI)	2.79 [0.62, 12.67]
2.2 Adults	11	1895	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.88, 1.19]

Comparison 3. Subgroup analysis ‐ children versus adults

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Comparison 4. Subgroup analysis ‐ length of ventilation

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Artificial airway occlusion Show forest plot	15		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Medium‐term	8	1031	Risk Ratio (M‐H, Random, 95% CI)	1.74 [0.41, 7.30]
1.2 Long‐term	7	1140	Risk Ratio (M‐H, Random, 95% CI)	1.47 [0.34, 6.36]
2 All‐cause mortality Show forest plot	11		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Medium‐term	5	860	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.78, 1.31]
2.2 Long‐term	6	1048	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.85, 1.25]
3 Pneumonia Show forest plot	11		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

3.1 Medium‐term	5	892	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.77, 1.47]
3.2 Long‐term	6	1036	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.59, 1.43]

Comparison 4. Subgroup analysis ‐ length of ventilation

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Comparison 5. Subgroup analysis ‐ hygroscopic versus hydrophobic heat and moisture exchanger (HME)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Artificial airway occlusion Show forest plot	15		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Hydrophobic	5	540	Risk Ratio (M‐H, Random, 95% CI)	2.86 [0.65, 12.62]
1.2 Hygroscopic	11	1638	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.32, 2.48]
2 All‐cause mortality Show forest plot	11		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Hydrophobic	2	189	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.46, 1.35]
2.2 Hygroscopic	9	1719	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.89, 1.23]
3 Pneumonia Show forest plot	12		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

3.1 Hydrophobic	3	469	Risk Ratio (M‐H, Random, 95% CI)	0.48 [0.28, 0.82]
3.2 Hygroscopic	9	1678	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.77, 1.17]

Comparison 5. Subgroup analysis ‐ hygroscopic versus hydrophobic heat and moisture exchanger (HME)

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Comparison 6. Heat and moisture exchanger (HME) with and without filters

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Artificial airway occlusion Show forest plot	15		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 With filter	8	1203	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.41, 3.80]
1.2 No filter	7	968	Risk Ratio (M‐H, Random, 95% CI)	2.46 [0.33, 18.47]
2 All‐cause mortality Show forest plot	12		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 With filter	5	1080	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.82, 1.22]
2.2 No filter	7	871	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.85, 1.36]
3 Pneumonia Show forest plot	13		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

3.1 With filter	5	979	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.76, 1.24]
3.2 no filter	8	1272	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.55, 1.38]

Comparison 6. Heat and moisture exchanger (HME) with and without filters

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Comparison 7. Sensitivity analyses ‐ selection bias

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality Show forest plot	12		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 Low risk of bias	2	286	Risk Ratio (M‐H, Random, 95% CI)	1.31 [0.91, 1.90]
1.2 Unknown risk of bias	10	1665	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.83, 1.16]
2 Pneumonia Show forest plot	13		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Low risk of bias	3	566	Risk Ratio (M‐H, Random, 95% CI)	0.72 [0.41, 1.28]
2.2 Unknown risk of bias	9	1582	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.77, 1.33]
2.3 High risk of bias	1	103	Risk Ratio (M‐H, Random, 95% CI)	1.10 [0.23, 5.21]

Comparison 7. Sensitivity analyses ‐ selection bias

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Comparison 8. Sensitivity analyses ‐ detection bias

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Artificial airway occlusion Show forest plot	15	2171	Risk Ratio (M‐H, Random, 95% CI)	1.59 [0.60, 4.19]

1.1 Low risk of bias	2	590	Risk Ratio (M‐H, Random, 95% CI)	0.14 [0.01, 2.74]
1.2 Unclear risk of bias	13	1581	Risk Ratio (M‐H, Random, 95% CI)	1.92 [0.69, 5.34]
2 Pneumonia Show forest plot	12		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

2.1 Low risk of bias	4	648	Risk Ratio (M‐H, Random, 95% CI)	0.84 [0.52, 1.36]
2.2 Unknown risk of bias	8	1500	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.70, 1.33]

Comparison 8. Sensitivity analyses ‐ detection bias

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